Acta Pharmacologica Sinica 2005 February; 26 (2): 166-170; doi: 10.1111/j.1745-7254.2005.00028.x

Aim: To investigate whether the amlodipine derivatives, CJX1 and CJX2, have a modulative effect on P-glycoprotein (P-gp) function in rat brain microvessel endothelial cells (RBMEC).

Methods: Isolated RBMEC were cultured in DMEM/F12 (1:1) medium. The amount of intracellular rhodamine (Rh123) was determined, using a fluorescence spectrophotometer, to evaluate the function of P-gp.

Results: The accumulation of Rh123 in RBMEC was potentiated in a concentration- dependent manner after incubation with CJX1 and CJX2 at 1, 2.5, 5, and 10 mmol/L (P<0.01), but no accumulation of Rh123 was observed in human umbilical vein endothelial cells after incubation with CJX1 and CJX2 10 mmol/L (P>0.05). Accumulation of intracellular Rh123 was increased and efflux of intracellular Rh123 was decreased in a time-dependent manner from 0-100 min after CJX1 and CXJ2 at 10 mmol/L treatment. The inhibitory effect of CJX1 and CJX2 on P-gp function was reversible and remained even at 120 min after removal of CJX1 and CJX2 at 2.5 mmol/L from the medium.

Conclusion: CJX1 and CJX2 exhibited a potent effect in the inhibition of P-gp function in vitro.

Keywords: amlodipine derivatives; CJX1; CJX2; verapamil; P-glycoprotein; blood brain barrier; vascular endothelium